Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Chen, P.; Chen, F.; Zhou, Benhong

doi:10.1111/ced.13751

Cited by 21 publications

(22 citation statements)

References 38 publications

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“…Overall, BRAF/MEKi‐induced SCARs seem to be infrequent. Likewise, AEGP and GBFE are not usually related to targeted therapies for melanoma 35–41 . Here, all but one patients had an indication of BRAF/MEKi for unresectable or metastatic melanoma; nonetheless, similar cutaneous adverse events have been described in patients under another indication 30,47 .…”

Section: Discussionmentioning

confidence: 78%

“…Almost all the patients undergoing BRAF/MEKi treatment experience some kind of adverse event 34 . Several BRAF/MEKi‐cutaneous adverse events have been described; among them, photosensitivity, pruritus and rash are the most frequent ones, appearing in up to 64% of patients 35–44 . The cutaneous side‐effect of greatest concern is the onset of skin tumours, specifically squamous cell carcinomas, appearing in 20‐30% of the patients 45 .…”

Section: Discussionmentioning

confidence: 99%

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Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

Torres‐Navarro

Unamuno‐Bustos

Botella‐Estrada

2020

Acad Dermatol Venereol

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Severe cutaneous adverse reactions (SCARs) [Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF‐mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi‐induced SCARs. A systematic search of the following terms: ‘vemurafenib’, ‘cobimetinib’, ‘dabrafenib’, ‘trametinib’, ‘encorafenib’, ‘binimetinib’, ‘Acute Generalized Exanthematous Pustulosis’, ‘Stevens Johnson syndrome’, ‘Toxic Epidermal Necrolysis’, ‘Generalized Bullous Fixed Eruption’ ‘Drug Hypersensitivity Syndrome’, and ‘DRESS’ in simple combination (every drug with each disease) and all in combination, was performed on MEDLINE, EMBASE, Web of Knowledge and The Cochrane Library repositories, with no restriction on language, for original studies. One hundred sixty‐eight original articles were found, 26 (retrospective series, case reports and conference abstracts) were selected, and 21 were included in the qualitative synthesis. A total of 31 SCAR cases (23 DRESS and 8 SJS/TEN – 1 SJS and 7 TEN –) were identified. Vemurafenib was the culprit drug in all but one case, which was dabrafenib‐induced. Mean time to SCAR onset from drug intake was 15.5 and 11.4 days, for SJS/TEN and DRESS, respectively. For the DRESS cases, hepatic involvement occurred in 96% and renal alterations in 87% of patients. Overall, BRAF/MEKi‐induced SCARs are rare. Among them, vemurafenib is the drug that requires more close monitoring for SCARs. Prior immunotherapy can favour SCARs. Vemurafenib DRESS is likely to occur within the first fifteen days of treatment accompanied by hepatic and renal involvement. Following vemurafenib‐induced SCAR resolution, switching to dabrafenib seems to be a safe alternative for these patients’ treatment.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

Torres‐Navarro

Unamuno‐Bustos

Botella‐Estrada

2020

Acad Dermatol Venereol

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“…Patients on EGFR inhibitors often experience extensive and severe reactions, e.g., acneiform eruptions (>2/3; severity grades 3–4 in 10–20%) 12,13,14,15 . Also BRAF inhibitors may cause a wide range of CSE, such as maculopapular rash (45%; 12% high‐grade rash), phototoxicity (30%), and squamoproliferative lesions, like eruptive keratoacanthomas and squamous cell carcinomas 16 . These are examples which cause dermatologists much more problems than those encountered with CPIs.…”

Section: Discussionmentioning

confidence: 99%

“…This differential finding reconfirms and extends the results of previous studies. 5,6,17,18 Although ipilimumab therapy is frequently prescribed as an additional treatment together with a PD1 blocker to gain more efficacy, this may result in more extensive toxicity in a selection of cases. Hence, the addition of ipilimumab to PD1 blockade as monotherapy should preferably be outweighed in terms of risk and accessory benefit for the individual patient.…”

Section: Discussionmentioning

confidence: 99%

Dermatological side effects rarely interfere with the continuation of checkpoint inhibitor immunotherapy for cancer

Rovers

Bovenschen

2020

Int J Dermatology

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Background Immunotherapy with checkpoint inhibitors (CPIs) is an emerging anticancer treatment strategy, which may cause a variety of skin reactions. In this study, we sought to analyze and classify the cutaneous side effects (CSE) of the CPIs nivolumab, pembrolizumab, and ipilimumab with respect to prevalence, type, and severity, and to review their potential interference with CPI immunotherapy. Methods In this retrospective analysis, medical records were analyzed with respect to incidence, type, and severity of CSE in patients on CPI immunotherapy for cancer. The implications for immunotherapy maintenance were scrutinized. Results From 2012 to 2019, 352 consecutive patients were treated with CPIs for cancer, of which 46 patients (13.1%) experienced CSE. The incidence of CSE was less with nivolumab (n = 16; 9.5%) and pembrolizumab monotherapy (n = 9; 9.6%) as compared to ipilimumab (n = 10; 23.3%) and combination therapy (n = 11; 23.9%); P < 0.05. Skin toxicity could be stratified by rash/eczema (n = 28; 60.9%), autoimmune (n = 8; 17.4%, vitiligo n = 5, lichen sclerosus n = 2, psoriasis guttata n = 1), lichenoid reaction (n = 5; 10.9%), pruritus (n = 4; 8.7%), and a miscellaneous group (n = 3; 6.5%). The limited severity grades of CSE caused immunotherapy disruption in only three (0.9%) cases. Interestingly, 80% of melanoma patients who developed vitiligo during immunotherapy had stable disease or disease remission. Conclusion CPIs in cancer patients may result in a distinct set of CSE, with drug rash and eczematous rash being the most common. CTLA-4 blocker ipilimumab and combination therapy are more prone to elicit skin toxicity than the PD-1 inhibitors nivolumab and pembrolizumab, although this rarely interferes with the continuation of immunotherapy.

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“…Furthermore, multiple KA may appear in younger ages within the framework of syndromic KA forms, like the Ferguson-Smith syndrome. More recent interest for novel treatment modalities for KA has revived as KA emerges as an important toxicity event of the vemurafenib [2] and probably also of the pembrolizumab [3] treatment in patients with advanced malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

Cryosurgery, Intralesional Methotrexate and Imiquimod for Keratoacanthoma: Tuning the Combination

Gaitanis

Bassukas

2019

Case Reports in Dermatological Medicine

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Keratoacanthomas (KA) are self-regressing, destructively expanding keratinocyte skin neoplasms typically characterized by sudden onset of explosive growth followed by complete involution. Cryosurgery, intralesional methotrexate and imiquimod have been used alone or in combination of two for the treatment of KA. Presently 3 patients (49, 60, and 65 years old; two females, one suspected with Ferguson-Smith syndrome), with 5 KA (6–24 mm maximal diameter) were treated with the combination of cryosurgery (liquid N2, open spray, 2 cycles of 15 sec each) and intralesional methotrexate (2.5–30 mg cumulative dose) and subsequent daily application of imiquimod (14–35 days). Starting with 4 cryosurgery/intralesional methotrexate sessions and 5 weeks daily imiquimod, to document feasibility and efficacy we progressively reduced the intensity of the treatment to one cryosurgery/intralesional methotrexate (total dose: 5 mg) session and 14 days of daily imiquimod without compromising efficacy. KA stopped growing promptly with sustained clearance after 6–24 months follow up, implicating a huge potential of therapeutic synergy of the employed modalities in the management of KA. We suggest that, optimized, the present three modalities combination (one session mild cryosurgery/low dose, 5 mg intralesional methotrexate and 2 weeks once daily imiquimod) is a promising treatment for KA that merits evaluation in further studies.

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Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Cited by 21 publications

References 38 publications

Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

Dermatological side effects rarely interfere with the continuation of checkpoint inhibitor immunotherapy for cancer

Cryosurgery, Intralesional Methotrexate and Imiquimod for Keratoacanthoma: Tuning the Combination

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